TABLE 1.
Characteristics of included studies
| Study | Strain and species | Brain injury model | Control for brain injury procedure | Age injury induced | Cell type | Total cells per dose | Cell administration time post‐injury | Administration route and details of location if relevant | Immunosuppression | Comparator |
|---|---|---|---|---|---|---|---|---|---|---|
| Braccioli 2017 (a) 28 | C57BL/6J mice | HI, right common carotid artery ligation and 10% O2 for 45 min | Sham surgery, anesthesia, and incision only | PND9 | Mouse fetal tissue NSCs | 1 × 105 | 10 days | Intracerebral injection into the ipsilateral hippocampus | No | Injury + saline |
| Braccioli 2017 (b) 29 | C57BL/6J mice | HI, right common carotid artery ligation and 10% O2 for 45 min | Sham surgery, anesthesia, and incision only | PND9 | Mouse fetal tissue NSCs +/− FOXP1 KO | 1 × 105 | 10 days | Intracerebral injection into the ipsilateral hippocampus | No | Injury + saline |
| Chau 2014 30 | Wistar rats | Focal cerebral ischemic injury, anesthetized with hypothermia and ligation of right middle cerebral artery | Sham surgery, hypothermia, and incision only | PND7 | Mouse iPSC‐derived NPCs | 4 × 105 | 7 days | Intracerebral injections at four sites in the peri‐infarct region | No | Injury + media |
| Comi 2008 31 | CD1 mice | Ischemic injury, right common carotid artery ligation, no hypoxia | Sham surgery, anesthesia, and incision only | PND12 | Mouse ESC‐derived NPCs | 1 × 105 | 2 or 7 days | Intracerebral injection into striatum, hemisphere not specified | No | Injury + vehicle a |
| Daadi 2010 32 | SD rats | HI, left common carotid artery ligation and 8% O2 for 90 min | No sham control | PND7 | Human ESC‐derived NPCs | 3 × 105 | 1 day | Intracerebral injections into three sites of the ipsilateral hemisphere | No | Injury + vehicle a |
| Ji 2015 33 | SD rats | HI, left common carotid artery ligation and 7.8% O2 for 120 min | Sham surgery, without ligation nor hypoxia | PND7 | Human fetal tissue NSCs | 3 × 105 | 1 day | Intranasal | No | Injury + saline |
| Kim 2018 34 | SD rats | HI + inflammation, left common carotid artery ligation and 8% O2 for 120 min followed by IP injection of LPS | Sham surgery, exposure of the artery without occlusion and vehicle treatment | PND7 | Human fetal tissue NSCs differentiated to OPCs |
4 × 105 (single dose) OR 1.6 × 106 (repeated doses) |
3 days (single dose) OR 3, 10, 20 and 30 days (repeated doses) | Intraventricular injections into four regions, hemisphere not specified | No | Injury + no vehicle |
| Li 2015 35 | SD rats | HI, left common carotid artery ligation and 8% O2 for 150 min | No sham control | PND7 | Human fetal tissue NSCs | 2.5 × 105 | 7 days | Intracerebral injection into the ipsilateral ventricle | No | Injury + saline |
| Rumajogee 2018 36 | C57Bl/6 mice | HI, right common carotid artery ligation and 8% O2 for 45 min | Sham surgery, no carotid occlusion was performed but still exposed to hypoxia | PND7 | Mouse adult tissue NPCs | 2.5 × 105 | 14 days | Intracerebral injection into the ipsilateral corpus callosum | Yes, cyclosporine | Injury + vehicle a |
| Sato 2008 37 | SD rats | HI, right common carotid artery ligation and 8% O2 for 120 min | No sham control | PND7 | Rat fetal tissue NSCs +/− chABC | 2.5 × 105 | 1 day | Intraventricular injection into the ipsilateral ventricle | No | Injury + saline |
| Shin 2018 38 | ICR mice | HI, right common carotid artery ligation and 8% O2 for 90 min | Sham surgery, anesthesia, and incision only | PND7 | Human fetal tissue NSCs +/− scaffold | 9.6 × 105 | 7 days | Intracerebral injection into the ipsilateral infarct cavity | Yes, cyclosporine | Injury + media |
| Shinoyama 2013 39 | ICR mice | HI, right carotid artery ligation and 8% O2 for 20 min | Sham surgery, opening skin of skull only | PND2 | Mouse ESC‐derived NPCs | 2 × 105 | 2 days | Intracerebral injection into the ipsilateral cerebral cortex | No | Injury + no vehicle |
| Tan 2014 40 | SD rats | HI, left common carotid artery ligation and 8% O2 for 120 min | Sham surgery, anesthesia, and incision only | PND7 | Rat fetal tissue NSCs +/− VEGF | 1 × 105 | 3 days | Intracerebral injection into the ipsilateral sensorimotor cortex | No | Injury + saline |
| Titomanlio 2011 41 | WT Swiss mice | Excitotoxic, intracerebral injection of ibotenate into right hemisphere | PBS injection | PND5 | Mouse fetal tissue NSCs | 3 × 105 | 4 hours OR 72 hours | Intraventricular injection into the contralateral ventricle | No | Injury + fibroblasts or saline |
| Wang 2014 42 | C57/BL6 mice | HI, right common carotid artery ligation and 8% O2 for 90 min | Anesthesia only | PND7 | Mouse fetal tissue NSCs +/− hypothermia | 3 × 105 | 1 day | Intracerebral injection into the ipsilateral ventricle | No | Injury + no vehicle |
| Yao 2016 43 | SD rats | HI, left carotid artery ligation and 8% O2 for 120 min | Sham surgery, anesthesia, and incision only | PND7 | Rat fetal tissue NSCs +/− VEGF | 1 × 105 | 3 days | Intracerebral injection into the ipsilateral sensorimotor cortex | No | Injury + saline |
| Ye 2018 44 | ICR mice | HI, right common carotid artery ligation and 10% O2 for 45 min | Sham surgery, anesthesia, and incision only | PND9 | Mouse fetal tissue NSCs +/− bFGF | 1 × 106 | 3 days | Intranasal | No | Injury + vehicle a |
| Zheng 2012 45 | SD rats | HI, left common carotid artery ligation and 8% O2 for 120 min | Sham surgery, anesthesia, and incision only | PND7 | Rat fetal tissue NSCs +/− VEGF | 1 × 105 | 3 days | Intracerebral injection into the ipsilateral somatosensory cortex | No | Injury + saline |
Abbreviations: bFGF, basic fibroblast growth factor; chABC, chondroitinase ABC; FOXP1, Forkhead Box P1; HI, hypoxic ischemic; IP, intraperitoneal; iPSCs, induced pluripotent stem cells; KO, knockout; LPS, lipopolysaccharide; NDPs, neurosphere derived precursor cells; NPCs, neural progenitor cells; NSCs, neural stem cells; NSPCs, neural stem progenitor cells; O2, oxygen; OPCs, oligodendrocyte progenitor cells; PBS, phosphate buffered saline; PND, postnatal day; SD, Sprague‐Dawley; VEGF, vascular endothelial growth factor; WT, wildtype.
a
Vehicle not specified.